Natalie D. Luscombe-Marsh

Protein-induced satiety: Effects and mechanisms of different proteins

Relatively high protein diets, i.e. diets that maintain the absolute number of grams of protein ingested as compared to before dieting, are a popular strategy for weight loss and weight maintenance. Research into multiple mechanisms regulating body weight has focused on the effects of different quantities and types of dietary protein. Satiety and energy expenditure are important in protein-enhanced weight loss and weight maintenance. Protein-induced satiety has been shown acutely, with single meals, with contents of 25% to 81% of energy from protein in general or from specific proteins, while subsequent energy intake reduction was significant. Protein-induced satiety has been shown with high protein ad libitum diets, lasting from 1 to 6 days, up to 6 months. Also significantly greater weight loss has been observed in comparison with control. Mechanisms explaining protein-induced satiety are nutrient-specific, and consist mainly of synchronization with elevated amino acid concentrations. Different proteins cause different nutrient related responses of (an)orexigenic hormones. Protein-induced satiety coincides with a relatively high GLP-1 release, stimulated by the carbohydrate content of the diet, PYY release, while ghrelin does not seem to be especially affected, and little information is available on CCK. Protein-induced satiety is related to protein-induced energy expenditure. Finally, protein-induced satiety appears to be of vital importance for weight loss and weight maintenance. With respect to possible adverse events, chronic ingestion of large amounts of sulphur-containing amino acids may have an indirect effect on blood pressure by induction of renal subtle structural damage, ultimately leading to loss of nephron mass, and a secondary increase in blood pressure. The established synergy between obesity and low nephron number on induction of high blood pressure and further decline of renal function identifies subjects with obesity, metabolic syndrome and diabetes mellitus II as particularly susceptible groups.

Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

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.

Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial

BACKGROUND Few well-controlled studies have comprehensively examined the effects of very-low-carbohydrate diets on type 2 diabetes (T2D). OBJECTIVE We compared the effects of a very-low-carbohydrate, high-unsaturated fat, low-saturated fat (LC) diet with a high-carbohydrate, low-fat (HC) diet on glycemic control and cardiovascular disease risk factors in T2D after 52 wk. DESIGN In this randomized controlled trial that was conducted in an outpatient research clinic, 115 obese adults with T2D [mean ± SD age: 58 ± 7 y; body mass index (in kg/m(2)): 34.6 ± 4.3; glycated hemoglobin (HbA1c): 7.3 ± 1.1%; duration of diabetes: 8 ± 6 y] were randomly assigned to consume either a hypocaloric LC diet [14% of energy as carbohydrate (carbohydrate <50 g/d), 28% of energy as protein, and 58% of energy as fat (<10% saturated fat)] or an energy-matched HC diet [53% of energy as carbohydrate, 17% of energy as protein, and 30% of energy as fat (<10% saturated fat)] combined with supervised aerobic and resistance exercise (60 min; 3 d/wk). Outcomes were glycemic control assessed with use of measurements of HbA1c, fasting blood glucose, glycemic variability assessed with use of 48-h continuous glucose monitoring, diabetes medication, weight, blood pressure, and lipids assessed at baseline, 24, and 52 wk. RESULTS Both groups achieved similar completion rates (LC diet: 71%; HC diet: 65%) and mean (95% CI) reductions in weight [LC diet: -9.8 kg (-11.7, -7.9 kg); HC diet: -10.1 kg (-12.0, -8.2 kg)], blood pressure [LC diet: -7.1 (-10.6, -3.7)/-6.2 (-8.2, -4.1) mm Hg; HC diet: -5.8 (-9.4, -2.2)/-6.4 (-8.4, -4.3) mm Hg], HbA1c [LC diet: -1.0% (-1.2%, -0.7%); HC diet: -1.0% (-1.3%, -0.8%)], fasting glucose [LC diet: -0.7 mmol/L (-1.3, -0.1 mmol/L); HC diet: -1.5 mmol/L (-2.1, -0.8 mmol/L)], and LDL cholesterol [LC diet: -0.1 mmol/L (-0.3, 0.1 mmol/L); HC diet: -0.2 mmol/L (-0.4, 0.03 mmol/L)] (P-diet effect ≥ 0.10). Compared with the HC-diet group, the LC-diet group achieved greater mean (95% CI) reductions in the diabetes medication score [LC diet: -0.5 arbitrary units (-0.7, -0.4 arbitrary units); HC diet: -0.2 arbitrary units (-0.4, -0.06 arbitrary units); P = 0.02], glycemic variability assessed by measuring the continuous overall net glycemic action-1 [LC diet: -0.5 mmol/L (-0.6, -0.3 mmol/L); HC diet: -0.05 mmol/L (-0.2, -0.1 mmol/L); P = 0.003], and triglycerides [LC diet: -0.4 mmol/L (-0.5, -0.2 mmol/L); HC diet: -0.01 mmol/L (-0.2, 0.2 mmol/L); P = 0.001] and greater mean (95% CI) increases in HDL cholesterol [LC diet: 0.1 mmol/L (0.1, 0.2 mmol/L); HC diet: 0.06 mmol/L (-0.01, 0.1 mmol/L); P = 0.002]. CONCLUSIONS Both diets achieved substantial weight loss and reduced HbA1c and fasting glucose. The LC diet, which was high in unsaturated fat and low in saturated fat, achieved greater improvements in the lipid profile, blood glucose stability, and reductions in diabetes medication requirements, suggesting an effective strategy for the optimization of T2D management. This trial was registered at www.anzctr.org.au as ACTRN12612000369820.

Monosodium glutamate is not associated with obesity or a greater prevalence of weight gain over 5 years: findings from the Jiangsu Nutrition Study of Chinese adults

Animal studies and one large cross-sectional study of 752 healthy Chinese men and women suggest that monosodium glutamate (MSG) may be associated with overweight/obesity, and these findings raise public concern over the use of MSG as a flavour enhancer in many commercial foods. The aim of this analysis was to investigate a possible association between MSG intake and obesity, and determine whether a greater MSG intake is associated with a clinically significant weight gain over 5 years. Data from 1282 Chinese men and women who participated in the Jiangsu Nutrition Study were analysed. In the present study, MSG intake and body weight were quantitatively assessed in 2002 and followed up in 2007. MSG intake was not associated with significant weight gain after adjusting for age, sex, multiple lifestyle factors and energy intake. When total glutamate intake was added to the model, an inverse association between MSG intake and 5 % weight gain was found (P = 0.028), but when the model was adjusted for either rice intake or food patterns, this association was abolished. These findings indicate that when other food items or dietary patterns are accounted for, no association exists between MSG intake and weight gain.

A Very Low Carbohydrate, Low Saturated Fat Diet for Type 2 Diabetes Management: A Randomized Trial

OBJECTIVE To comprehensively compare the effects of a very low-carbohydrate, high–unsaturated/low–saturated fat diet (LC) with those of a high–unrefined carbohydrate, low-fat diet (HC) on glycemic control and cardiovascular disease (CVD) risk factors in type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS Obese adults (n = 115, BMI 34.4 ± 4.2 kg/m2, age 58 ± 7 years) with T2DM were randomized to a hypocaloric LC diet (14% carbohydrate [<50 g/day], 28% protein, and 58% fat [<10% saturated fat]) or an energy-matched HC diet (53% carbohydrate, 17% protein, and 30% fat [<10% saturated fat]) combined with structured exercise for 24 weeks. The outcomes measured were as follows: glycosylated hemoglobin (HbA1c), glycemic variability (GV; assessed by 48-h continuous glucose monitoring), antiglycemic medication changes (antiglycemic medication effects score [MES]), and blood lipids and pressure. RESULTS A total of 93 participants completed 24 weeks. Both groups achieved similar completion rates (LC 79%, HC 82%) and weight loss (LC −12.0 ± 6.3 kg, HC −11.5 ± 5.5 kg); P ≥ 0.50. Blood pressure (−9.8/−7.3 ± 11.6/6.8 mmHg), fasting blood glucose (−1.4 ± 2.3 mmol/L), and LDL cholesterol (−0.3 ± 0.6 mmol/L) decreased, with no diet effect (P ≥ 0.10). LC achieved greater reductions in triglycerides (−0.5 ± 0.5 vs. −0.1 ± 0.5 mmol/L), MES (−0.5 ± 0.5 vs. −0.2 ± 0.5), and GV indices; P ≤ 0.03. LC induced greater HbA1c reductions (−2.6 ± 1.0% [−28.4 ± 10.9 mmol/mol] vs. −1.9 ± 1.2% [−20.8 ± 13.1 mmol/mol]; P = 0.002) and HDL cholesterol (HDL-C) increases (0.2 ± 0.3 vs. 0.05 ± 0.2 mmol/L; P = 0.007) in participants with the respective baseline values HbA1c >7.8% (62 mmol/mol) and HDL-C <1.29 mmol/L. CONCLUSIONS Both diets achieved substantial improvements for several clinical glycemic control and CVD risk markers. These improvements and reductions in GV and antiglycemic medication requirements were greatest with the LC compared with HC. This suggests an LC diet with low saturated fat may be an effective dietary approach for T2DM management if effects are sustained beyond 24 weeks.

Intraduodenal protein modulates antropyloroduodenal motility, hormone release, glycemia, appetite, and energy intake in lean men

BACKGROUND Intraduodenal fat and carbohydrate modulate antropyloroduodenal motility and hormone release and suppress appetite and energy intake in a load-dependent manner. Protein also suppresses energy intake, but its effects on these gastrointestinal factors and their role in the appetite-suppressive effects of protein remain unclear. OBJECTIVE We aimed to characterize the effects of different intraduodenal protein loads on antropyloroduodenal pressures, gastrointestinal hormone release, glucose and insulin concentrations, appetite perceptions, and energy intake. DESIGN Sixteen lean, healthy men were studied on 4 occasions in a randomized, double-blind fashion. Antropyloroduodenal pressures, plasma glucagon-like peptide 1 (GLP-1), cholecystokinin, peptide YY, ghrelin, blood glucose, serum insulin, and appetite were measured during 60-min, 4-mL/min intraduodenal infusions of protein at 0.5, 1.5, or 3 kcal/min or saline (control). Energy intakes at a buffet lunch consumed immediately after the infusion were quantified. RESULTS Increases in the load of protein resulted in greater suppression of antral motility, greater stimulation of basal and isolated pyloric pressures and plasma cholecystokinin and GLP-1 concentrations, and greater suppression of energy intake. However, energy intake was reduced only after a protein load of 3 kcal/min compared with after all other treatments (P < 0.05). The suppression of energy intake after adjustment for cholecystokinin, GLP-1, and insulin was related inversely with basal pyloric pressure (r = -0.51, P < 0.001). CONCLUSION The acute effects of intraduodenal protein on antropyloroduodenal motility, gastrointestinal hormone release, glucose, and insulin are load dependent and contribute to the suppression of energy intake. This trial was registered at www.anzctr.org.au as 12610000376044.

Long-term weight maintenance and cardiovascular risk factors are not different following weight loss on carbohydrate-restricted diets high in either monounsaturated fat or protein in obese hyperinsulinaemic men and women

The aim of this study was to determine after 52 weeks whether advice to follow a lower carbohydrate diet, either high in monounsaturated fat or low fat, high in protein had differential effects in a free-living community setting. Following weight loss on either a high monounsaturated fat, standard protein (HMF; 50 % fat, 20 % protein (67 g/d), 30 % carbohydrate) or a high protein, moderate fat (HP) (40 % protein (136 g/d), 30 % fat, 30 % carbohydrate) energy-restricted diet (6000 kJ/d) subjects were asked to maintain the same dietary pattern without intensive dietary counselling for the following 36 weeks. Overall weight loss was 6.2 (SD 7.3) kg (P < 0.01 for time with no diet effect, 7.6 (SD 8.1) kg, HMF v. 4.8 (SD 6.6) kg, HP). In a multivariate regression model predictors of weight loss at the end of the study were sex, age and reported percentage energy from protein (R2 0.22, P < 0.05 for the whole model). Fasting plasma insulin decreased (P < 0.01, with no difference between diets), 13.9 (SD 4.6) to 10.2 (SD 5.2) mIU/l, but fasting plasma glucose was not reduced. Neither total cholesterol nor LDL-cholesterol were different but HDL was higher, 1.19 (SD 0.26) v. 1.04 (SD 0.29) (P < 0.001 for time, no diet effect), while TAG was lower, 1.87 (SD 1.23) v. 2.22 (SD 1.15) mmol/l (P < 0.05 for time, no diet effect). C-reactive protein decreased (3.97 (SD 2.84) to 2.43 (SD 2.29) mg/l, P < 0.01). Food records showed that compliance to the prescribed dietary patterns was poor. After 1 year there remained a clinically significant weight loss and improvement in cardiovascular risk factors with no adverse effects of a high monounsaturated fat diet.

Sex differences in energy homeostatis following a diet relatively high in protein exchanged with carbohydrate, assessed in a respiration chamber in humans

CONTEXT Obesity prevalence is generally higher in women than in men, and a paucity of research with sex-specific approaches exists. The question arises whether current weight loss programmes, largely developed and tested on women, are appropriate for men. OBJECTIVE Investigate 24 h energy metabolism, satiety and related hormones during a diet relatively high in protein (HP), exchanged with carbohydrate compared to an adequate-protein (AP) diet, in a respiration chamber in men, in comparison with previous outcomes in women. DESIGN Ten healthy males (BMI: 22.5+/-1.6 kg/m(2), age: 25+/-3.5 y) were fed in energy balance with an AP (10/60/30% of energy of protein/carbohydrate/fat) or a HP (30/40/30% of energy of protein/carbohydrate/fat) diet in a randomized cross-over design. RESULTS During the HP diet, 24 h Energy Expenditure (10.5+/-0.5 vs 10.0+/-0.5 MJ/d; p<0.05), Sleeping Energy Expenditure (7.1+/-0.3 vs 6.9+/-0.2 MJ/d; p<0.05), protein balance (0.5+/-0.02 vs 0.0+/-0.01 MJ/d; p<0.05), satiety (AUC) p<0.05, and plasma GLP-1 concentrations (42+/-23 vs 28+/-16 AUC; p<0.005) were significantly higher and 24 h RQ (0.80 vs 0.85; p<0.01), fat balance (-0.85+/-0.03 vs 0.05 vs 0.03 MJ/d; p<0.01) and hunger (AUC) p<0.05, were significantly lower. Comparisons reveal a stronger reaction in men in energy expenditure and substrate oxidation, whereas satiety reacted stronger in the women. CONCLUSIONS Effects of a diet relatively high in protein exchanged with carbohydrate, vs an adequate protein diet are a stronger increased energy expenditure, fat oxidation, protein anabolism in men, and a stronger increased satiety in women, thereby creating sex-specific conditions for long-term use for body-weight management.

Effects of intraduodenal infusion of L-tryptophan on ad libitum eating, antropyloroduodenal motility, glycemia, insulinemia, and gut peptide secretion in healthy men.

CONTEXT Changes in gut motor and hormonal function contribute to the eating-inhibitory and glucose-lowering effects of protein. The effect of amino acids, the digestive products of protein, on gastrointestinal function, eating, and glycemia has not been investigated comprehensively. OBJECTIVE We tested the hypothesis that L-tryptophan (L-Trp) stimulates gastrointestinal motor and hormonal functions, inhibits eating, and modulates glycemia. Design, Settings, Participants, and Intervention: Ten healthy, normal-weight men were studied in randomized, double-blind fashion, each receiving a 90-minute intraduodenal infusion of L-Trp at 0.075 (total 6.75 kcal) or 0.15 (total 13.5 kcal) kcal/min or saline (control). MAIN OUTCOME MEASURES Antropyloroduodenal motility, plasma ghrelin, cholecystokinin, glucagon-like peptide-1, peptide tyrosine tyrosine, insulin, glucagon, blood glucose, and appetite perceptions were measured. Food intake was quantified from a buffet meal after the infusion. RESULTS Intraduodenal L-Trp suppressed antral pressures (P < .05) and stimulated pyloric pressures (P < .01) and markedly increased cholecystokinin and glucagon (both P < .001). Glucagon-like peptide-1 and peptide tyrosine tyrosine increased modestly (both P < .001), but there was no effect on total ghrelin. Insulin increased slightly (P < .05) without affecting blood glucose. Plasma L-Trp increased substantially (P < .001). All effects were dose-related and associated with increased fullness and substantially decreased energy intake (P < .001). There was a strong inverse correlation between energy intake and plasma L-Trp (r = -0.70; P < .001). CONCLUSIONS Low caloric intraduodenal loads of L-Trp affect gut motor and hormonal function and markedly reduce energy intake. A strong inverse correlation between energy intake and plasma L-Trp suggests that, beyond gut mechanisms, direct effects of circulating L-Trp mediate its eating-inhibitory effect.