Effects of two consecutive mixed meals high in palmitic acid or stearic acid on 8-h postprandial lipemia and glycemia in healthy-weight and overweight men and postmenopausal women: a randomized controlled trial.

PURPOSE: Palmitic and stearic acids have different effects on fasting serum lipoproteins. However, the effects on postprandial lipemia and glycemia are less clear. Also, the effects of a second meal may differ from those of the first meal. Therefore, we studied the effects of two consecutive mixed meals high in palmitic acid- or stearic acid-rich fat blends on postprandial lipemia and glycemia. METHODS: In a randomized, crossover study, 32 participants followed 4-week diets rich in palmitic or stearic acids, At the end of each dietary period, participants consumed two consecutive meals each containing ± 50 g of the corresponding fat blend. RESULTS: Postprandial concentrations of triacylglycerol (diet-effect: - 0.18 mmol/L; p = 0.001) and apolipoprotein B48 (diet-effect: - 0.68 mg/L; p = 0.002) were lower after stearic-acid than after palmitic-acid intake. Consequently, total (iAUC0-8 h) and first meal (iAUC0-4 h) responses were lower after stearic-acid intake (p ≤ 0.01). Second meal responses (iAUC4-8 h) were not different. Postprandial changes between the diets in non-esterified fatty acids (NEFA) and C-peptide differed significantly over time (p < 0.001 and p = 0.020 for diet*time effects, respectively), while those for glucose and insulin did not. The dAUC0-8 h, dAUC0-4 h, and dAUC4-8 h for NEFA were larger after stearic-acid intake (p ≤ 0.05). No differences were observed in the iAUCs of C-peptide, glucose, and insulin. However, second meal responses for glucose and insulin (iAUC4-8 h) tended to be lower after stearic-acid intake (p < 0.10). CONCLUSION: Consumption of the stearic acid-rich meals lowered postprandial lipemia as compared with palmitic acid. After the second stearic acid-rich meal, concentrations of C-peptide peaked earlier and those of NEFA decreased more. Clinical trial registry This trial was registered at clinicaltrials.gov as NCT02835651 on July 18, 2016.

Dietary stearic acid and palmitic acid do not differently affect ABCA1-mediated cholesterol efflux capacity in healthy men and postmenopausal women: A randomized controlled trial.

BACKGROUND: The saturated fatty acid stearic acid (C18:0) lowers HDL cholesterol compared with palmitic acid (C16:0). However, the ability of HDL particles to promote cholesterol efflux from macrophages (cholesterol efflux capacity; CEC) may better predict coronary heart disease (CHD) risk than HDL cholesterol concentrations. OBJECTIVE: We examined effects of exchanging dietary palmitic acid for stearic acid on ATP-binding cassette transporter A1 (ABCA1)-mediated CEC, and other conventional and emerging cardiometabolic risk makers. DESIGN: In a double-blind, randomized, crossover study with two 4-week isocaloric intervention periods, 34 healthy men and postmenopausal women (61.5 ± 5.7 years, BMI: 25.4 ± 2.5 kg/m2) followed diets rich in palmitic acids or stearic acids. Difference in intakes was 6% of daily energy. ABCA1-mediated CEC was measured from J774 macrophages to apolipoprotein (apo)B-depleted serum. RESULTS: Compared with the palmitic-acid diet, the stearic-acid diet lowered serum LDL cholesterol (-0.14 mmol/L; p = 0.010), HDL cholesterol (-0.09 mmol/L; p=<0.001), and apoA1 (-0.05 g/L; p < 0.001). ABCA1-mediated CEC did not differ between diets (p = 0.280). Cholesteryl ester transfer protein (CETP) mass was higher on stearic acid (0.11 mg/L; p = 0.003), but CETP activity was comparable. ApoB100 did not differ, but triacylglycerol concentrations tended to be higher on stearic acid (p = 0.100). Glucose concentrations were comparable. Effects on insulin and C-peptide were sex-dependent. In women, the stearic-acid diet increased insulin concentrations (1.57 µU/mL; p = 0.002), while in men, C-peptide concentrations were lower (-0.15 ng/mL; p = 0.037). Interleukin 6 (0.15 pg/mL; p = 0.039) and tumor necrosis factor alpha (0.18 pg/mL; p = 0.005), but not high-sensitivity C-reactive protein, were higher on stearic acid. Soluble intracellular adhesion molecule (9 ng/mL; p = 0.033), but not soluble vascular cell adhesion molecule and endothelial-selectin concentrations decreased after stearic-acid consumption. CONCLUSIONS: As expected, stearic-acid intake lowered LDL cholesterol, HDL cholesterol, and apoA1. Insulin sensitivity in women and low-grade inflammation might be unfavorably affected by stearic-acid intake. However, palmitic-acid and stearic-acid intakes did not differently affect ABCA1-mediated CEC. CLINICAL TRIAL REGISTRY: This trial was registered at clinicaltrials.gov as NCT02835651.

Plant-derived polyunsaturated fatty acids and markers of glucose metabolism and insulin resistance: a meta-analysis of randomized controlled feeding trials.

The objective of this meta-analysis was to investigate the effects of plant-derived polyunsaturated fatty acids (PUFAs) on glucose metabolism and insulin resistance. Scopus and PubMed databases were searched until January 2018. Eligible studies were randomized controlled feeding trials that investigated the effects of a diet high in plant-derived PUFA as compared with saturated fatty acids (SFA) or carbohydrates and measured markers of glucose metabolism and insulin resistance as outcomes. Data from 13 relevant studies (19 comparisons of plant-derived PUFA with control) were retrieved. Plant-derived PUFA did not significantly affect fasting glucose (-0.01 mmol/L (95 % CI - 0.06 to 0.03 mmol/L)), but lowered fasting insulin by 2.6 pmol/L (-4.9 to -0.2 pmol/L) and homeostatic model assessment-insulin resistance (HOMA-IR) by 0.12 units (-0.23 to - 0.01 units). In dose-response analyses, a 5% increase in energy (En%) from PUFA significantly reduced insulin by 5.8 pmol/L (95% CI -10.2 to -1.3 pmol/L), but not glucose (change -0.07, 95% CI -0.17 to 0.04 mmol/L) and HOMA-IR (change - 0.24, 95% CI -0.56 to 0.07 units). In subgroup analyses, studies with higher PUFA dose (upper tertiles) reduced insulin (-6.7, -10.5 to -2.9 pmol/L) and HOMA-IR (-0.28, -0.45 to -0.12 units), but not glucose (-0.09, 95% CI -0.18 to 0.01 mmol/L), as compared with an isocaloric control. Subgroup analyses showed no differences in effects between SFA and carbohydrates as replacement nutrients (p interaction ≥0.05). Evidence from randomized controlled trials indicated that plant-derived PUFA as an isocaloric replacement for SFA or carbohydrates probably reduces fasting insulin and HOMA-IR in populations without diabetes.

A low-fat spread with added plant sterols and fish omega-3 fatty acids lowers serum triglyceride and LDL-cholesterol concentrations in individuals with modest hypercholesterolaemia and hypertriglyceridaemia.

PURPOSE: The primary and secondary objectives were to investigate the triglyceride (TG) and LDL-cholesterol (LDL-C) lowering effects of a spread with added plant sterols (PS) and fish oil as compared to a placebo spread. METHODS: This study had a randomized, double-blind, placebo-controlled, parallel group design with two intervention arms. Following a 2-week placebo run-in period, 260 healthy individuals with modestly elevated blood TG (≥ 1.4 mmol/L) and LDL-C (≥ 3.4 mmol/L) concentrations consumed either the placebo or intervention spread for 4 weeks. The intervention spread contained 2.0 g/day PS and 1.0 g/day eicosapentaenoic acid (EPA) + docosahexanoic acid (DHA) from fish oil. Fasting serum lipids and apolipoproteins (Apo) (exploratory) were measured at the end of the run-in and intervention phases. RESULTS: Four-week consumption of the intervention spread resulted in significantly lower TG (- 10.6%, 95% CI - 16.0 to - 4.9%; P < 0.001) and LDL-C concentrations (- 5.2%; 95% CI - 7.8 to - 2.4%) as compared to placebo. Total cholesterol (- 3.9%; 95% CI - 6.1 to - 1.5%), non-HDL-C (- 5.4%; 95% CI - 8.1 to - 2.7%), remnant-cholesterol (- 8.1%; 95% CI - 3.4 to - 12.5%), ApoAII (- 2.9%; 95% CI - 5.5 to - 0.2%), ApoCIII (- 7.7%; 95% CI - 12.1 to - 3.1%) and ApoB (- 3.2%; 95% CI - 5.9 to - 0.4%) concentrations were also significantly lower, as compared to placebo. No significant treatment effects were found for HDL-cholesterol, ApoAI, ApoCII, Apo E or ApoB/ApoAI. CONCLUSIONS: Four-week consumption of the intervention spread led to significant and clinically relevant decreases in serum TG, LDL-C and other blood lipid concentrations. The study was registered at clinicaltrials.gov (NCT02728583).

Progressing Insights into the Role of Dietary Fats in the Prevention of Cardiovascular Disease.

Dietary fats have important effects on the risk of cardiovascular disease (CVD). Abundant evidence shows that partial replacement of saturated fatty acids (SAFA) with unsaturated fatty acids improves the blood lipid and lipoprotein profile and reduces the risk of coronary heart disease (CHD). Low-fat diets high in refined carbohydrates and sugar are not effective. Very long-chain polyunsaturated n-3 or omega-3 fatty acids (n-3 VLCPUFA) present in fish have multiple beneficial metabolic effects, and regular intake of fatty fish is associated with lower risks of fatal CHD and stroke. Food-based guidelines on dietary fats recommend limiting the consumption of animal fats high in SAFA, using vegetable oils high in monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and eating fatty fish. These recommendations are part of a healthy eating pattern that also includes ample intake of plant-based foods rich in fiber and limited sugar and salt.

The effect of two weeks ingestion of a bitter tastant mixture on energy intake in overweight females.

Triggering of gastro-intestinal bitter taste receptors might have implications for appetite and food intake, but the evidence in humans is mixed and limited to acute studies. We previously reported that 15-days consumption of drinks with purified Hoodia gordonii extract and its taste-matched control both produced similar, significant energy intake (EI) reductions in females in an in-patient setting, with no significant differences between treatments. In that study the control was matched to Hoodia flavour and bitterness using Raisin Flavour (RF), Sucrose Octa Acetate (SOA) and Quassia Extract (QE). As triggering of gastrointestinal bitter receptors might have produced shared effects on EI, our objective here was to assess the effects of sustained exposure to capsules containing the same bitter RF + SOA + QE mix itself on EI, compared to a non-bitter placebo. In this randomized, double-blind study, sixty slightly overweight women in parallel groups consumed twice-daily capsules without (placebo) or with the tastant mixture (0.88 mg SOA, 0.088 mg QE, 0.22 mg RF) on days 1-14. On day 0 all subjects received placebo capsules at 0800 and 1600, ad libitum meals at 0900, 1300, 1700, and snacks after 1900. On day 14 these test procedures were repeated. Changes in EI on days 14 versus 0 between treatment groups were assessed using ANCOVA. Total EI differences on days 14 versus 0 were not significant (mean active-placebo treatment difference -109 kcal, SE 71, P = 0.13), nor was this significant when analyzed separately for each meal within the test day. Body weight changes were negligible. In conclusion, sustained exposure to these encapsulated bitter tastants did not significantly affect EI in overweight females.

Fat composition of vegetable oil spreads and margarines in the USA in 2013: a national marketplace analysis.

Worldwide, the fat composition of spreads and margarines ("spreads") has significantly changed over the past decades. Data on fat composition of US spreads are limited and outdated. This paper compares the fat composition of spreads sold in 2013 to that sold in 2002 in the USA. The fat composition of 37 spreads representing >80% of the US market sales volume was determined by standard analytical methods. Sales volume weighted averages were calculated. In 2013, a 14 g serving of spread contained on average 7.1 g fat and 0.2 g trans-fatty acids and provided 22% and 15% of the daily amounts recommended for male adults in North America of omega-3 α-linolenic acid and omega-6 linoleic acid, respectively. Our analysis of the ingredient list on the food label showed that 86% of spreads did not contain partially hydrogenated vegetable oils (PHVO) in 2013. From 2002 to 2013, based on a 14 g serving, total fat and trans-fatty acid content of spreads decreased on average by 2.2 g and 1.5 g, respectively. In the same period, the overall fat composition improved as reflected by a decrease of solid fat (from 39% to 30% of total-fatty acids), and an increase of unsaturated fat (from 61% to 70% of total-fatty acids). The majority of US spreads no longer contains PHVO and can contribute to meeting dietary recommendations by providing unsaturated fat.

Sustained satiety induced by food foams is independent of energy content, in healthy adults.

Our previous research demonstrated high, sustained satiety effects of stabilized food foams relative to their non-aerated compositions. Here we test if the energy and macronutrients in a stabilized food foam are critical for its previously demonstrated satiating effects. In a randomized, crossover design, 72 healthy subjects consumed 400 mL of each of four foams, one per week over four weeks, 150 min after a standardized breakfast. Appetite ratings were collected for 180 min post-foam. The reference was a normal energy food foam (NEF1, 280 kJ/400 mL) similar to that used in our previous research. This was compared to a very low energy food foam (VLEF, 36 kJ/400 mL) and 2 alternative normal energy foams (NEF2 and NEF3) testing possible effects of compositional differences other than energy (i.e. emulsifier and carbohydrate source). Appetite ratings were quantified as area under the curve (AUC) and time to return to baseline (TTRTB). Equivalence to NEF1 was predefined as the 90% confidence interval of between-treatment differences in AUC being within -5 to +5 mm/min. All treatments similarly affected appetite ratings, with mean AUC for fullness ranging between 49.1 and 52.4 mm/min. VLEF met the statistical criterion for equivalence to NEF1 for all appetite AUC ratings, but NEF2 and NEF3 did not. For all foams the TTRTB for satiety and fullness were consistently between 150 and 180 min, though values were shortest for NEF2 and especially NEF3 foams for most appetite scales. In conclusion, the high, sustained satiating effects of these food foams are independent of energy and macronutrient content at the volumes tested.

Formation of Plant Sterol Oxidation Products in Foods during Baking and Cooking Using Margarine without and with Added Plant Sterol Esters.

Plant sterols (PS) in foods are subject to thermal oxidation to form PS oxidation products (POP). This study measured POP contents of 19 foods prepared by typical household baking and cooking methods using margarines without (control) and with 7.5% added PS (as 12.5% PS-esters, PS-margarine). Median POP contents per portion size of cooked foods were 0.57 mg (range 0.05-1.11 mg) with control margarine versus 1.42 mg (range 0.08-20.5 mg) with PS-margarine. The oxidation rate of PS (ORP) was 0.50% (median) with the PS-margarine and 3.66% with the control margarine. Using the PS-margarine, microwave-cooked codfish had the lowest POP content, with 0.08 mg per portion, while shallow-fried potatoes had the highest POP content, 20.5 mg per portion. Median POP contents in cookies, muffins, banana bread, and sponge cake baked with the control or PS-margarine were 0.12 mg (range 0.11-0.21 mg) and 0.24 mg (range 0.19-0.60 mg) per portion, with a corresponding ORP of 1.38% and 0.06%, respectively. POP contents in all the cooked and baked foods did not exceed 20.5 mg per typical portion size. A wide variation in the distribution of individual POP among different foods existed, with 7-keto-PS and 5,6-epoxy-PS being the major oxidation products.

Aerated drinks increase gastric volume and reduce appetite as assessed by MRI: a randomized, balanced, crossover trial.

BACKGROUND: Compared with nonaerated, isocaloric controls, aerated foods can reduce appetite throughout an entire dieting day. Increased gastric volumes and delayed emptying are possible but unexplored mechanisms. OBJECTIVE: We tested the hypothesis that aerated drinks (foams) of differing gastric stability would increase gastric distension and reduce appetite compared with a control drink. DESIGN: In a randomized, balanced, crossover trial, 18 healthy male participants consumed the following 3 skimmed-milk-based test products (all 110 kcal): 2 drinks aerated to foams by whipping (to 490 mL), one drink that was stable in the stomach [stable foam (SF)], and one drink that was less stable in the stomach [less-stable foam (LSF)], and a nonaerated drink [liquid control (LC); 140 mL]. Over 4 h, stomach contents (foam, air, and liquid) were imaged using magnetic resonance imaging (MRI), and self-reported appetite ratings were collected and quantified by the area under the curve or time to return to baseline (TTRTB). RESULTS: Compared with the LC, both foams caused significantly increased gastric volumes and reduced hunger (all P < 0.001). Compared with the LSF, SF further produced a significantly slower decrease in the total gastric content (P < 0.05) and foam volume (P < 0.0001) and a longer TTRTB (197 compared with 248 min, respectively; P < 0.05), although the hunger AUC was not statistically different. Results for other appetite scales were similar. CONCLUSIONS: With this MRI trial, we provide novel insights on the gastrointestinal behavior of aerated drinks by measuring separate volumes of foam, liquid, and air layers in the stomach. Appetite suppression induced by foams could largely be explained by effects on gastric volumes and emptying, which may be further enhanced by foam stability. This trial was registered at clinicaltrials.gov as NCT01690182.

Effects of 15-d repeated consumption of Hoodia gordonii purified extract on safety, ad libitum energy intake, and body weight in healthy, overweight women: a randomized controlled trial.

BACKGROUND: Extracts from Hoodia gordonii have been shown to decrease food intakes and body weights in animals and were proposed as a food supplement or ingredient for weight management. OBJECTIVE: We assessed the safety and efficacy of a 15-d repeated consumption of H. gordonii purified extract (HgPE) relative to a placebo in humans. DESIGN: Healthy, overweight women, who were stratified by percentage body fat, received either HgPE (n = 25) or a placebo (n = 24) for 15 d. Subjects were resident in a clinic for a 4-d run-in period and a 15-d treatment period in which they received 2 servings/d of 1110 mg HgPE or a placebo formulated in a yogurt drink 1 h before breakfast and dinner. Subjects were otherwise allowed to eat ad libitum from standardized menus. RESULTS: There were no serious adverse events, but HgPE was less well tolerated than was the placebo because of episodes of nausea, emesis, and disturbances of skin sensation. Blood pressure, pulse, heart rate, bilirubin, and alkaline phosphatase showed significant (P < 0.05) increases in the HgPE group. Mean effects on ad libitum energy intakes and body weights did not differ significantly between the HgPE- and placebo-treatment groups (P > 0.05). CONCLUSIONS: In comparison with a matched placebo, the consumption of HgPE for 15 d appeared to be associated with significant adverse changes in some vital signs and laboratory parameters. HgPE was less well tolerated than was the placebo and did not show any significant effects on energy intakes or body weights relative to the placebo. This trial was registered at clinicaltrials.gov as NCT01306422.

Postprandial ghrelin responses are associated with the intermeal interval in time-blinded normal weight men, but not in obese men.

OBJECTIVE: To investigate the relation between ghrelin responses and meal initiation and the effects of BMI and energy status on this. DESIGN: The experiment had a randomised, cross-over design. SETTING AND SUBJECTS: Nine normal-weight (age: 33.2+/-4.8 y, BMI: 23.2+/-0.5 kg/m2) and eleven obese (age: 40.8+/- 4.7 y, BMI: 33.2+/-0.8 kg/m2) healthy men were recruited from a pool of volunteers and by advertisements. INTERVENTIONS: Subjects followed a three-day energy restrictive and a three-day energy balanced diet separated by one month. Each diet was followed by a time-blinded (overnight) stay at the research facility. Subjects received a breakfast (preload) and were instructed to ask for lunch when they felt hungry. Ghrelin, insulin, glucose, free fatty acids, appetite, IMI and energy intake during lunch were assessed. RESULTS: Postprandial decreases in ghrelin (r=-0.54; p<0.05) and the AUC of the ghrelin response (r=-0.57, p=0.01) were associated with the intermeal interval, independent of diet, but in normal weight subjects only. Lunch request was preceded by an increase in ghrelin, reaching at least 93% of fasting values. These preprandial increases in ghrelin were correlated with IMI, after energy restriction only. Ghrelin concentrations but not changes in ghrelin were correlated with appetite. CONCLUSION: Meal-related changes in ghrelin are correlated with the IMI in normal weight subjects only, independent of diet. Ghrelin concentrations may need to reach a certain threshold level before the next meal is initiated.

High-protein and high-carbohydrate breakfasts differentially change the transcriptome of human blood cells.

BACKGROUND: Application of transcriptomics technology in human nutrition intervention studies would allow for genome-wide screening of the effects of specific diets or nutrients and result in biomarker profiles. OBJECTIVE: The aim was to evaluate the potential of gene expression profiling in blood cells collected in a human intervention study that investigated the effect of a high-carbohydrate (HC) or a high-protein (HP) breakfast on satiety. DESIGN: Blood samples were taken from 8 healthy men before and 2 h after consumption of an HP or an HC breakfast. Both breakfasts contained acetaminophen for measuring the gastric emptying rate. Analysis of the transcriptome data focused on the effects of the HP or HC breakfast and of acetaminophen on blood leukocyte gene expression profiles. RESULTS: Breakfast consumption resulted in differentially expressed genes, 317 for the HC breakfast and 919 for the HP breakfast. Immune response and signal transduction, specifically T cell receptor signaling and nuclear transcription factor kappaB signaling, were the overrepresented functional groups in the set of 141 genes that were differentially expressed in response to both breakfasts. Consumption of the HC breakfast resulted in differential expression of glycogen metabolism genes, and consumption of the HP breakfast resulted in differential expression of genes involved in protein biosynthesis. CONCLUSIONS: Gene expression changes in blood leukocytes corresponded with and may be related to the difference in macronutrient content of the breakfast, meal consumption as such, and acetaminophen exposure. This study illustrates the potential of gene expression profiling in blood to study the effects of dietary exposure in human intervention studies.

Fasting ghrelin does not predict food intake after short-term energy restriction.

OBJECTIVE: To study the role of ghrelin as a hunger signal during energy restriction and to test the hypothesis that changes in fasting leptin concentrations during energy restriction are associated with changes in fasting ghrelin concentrations. RESEARCH METHODS AND PROCEDURES: Thirty-five healthy, lean men (23 +/- 3 years of age; BMI: 22.3 +/- 1.6 kg/m(2)) participated in a controlled intervention study. Fasting ghrelin and leptin concentrations were measured before and after 2 days of 62% energy restriction and after a 2-day period of ad libitum food intake. Energy intake during the latter period was assessed. RESULTS: On average, ghrelin concentrations did not change (0.05 mug/liter; 95% confidence interval, -0.03; 0.12) during energy restriction. Changes in ghrelin concentration during energy restriction were not associated with energy intake during the ad libitum period (r = 0.07; not significant). Ad libitum energy intake was, however, associated with the change in ghrelin concentrations during the same period (r = -0.34; p = 0.05). Ghrelin and leptin concentrations were not associated. In addition, the ratio of percentage changes in ghrelin and leptin during energy restriction was not correlated with ad libitum food intake after energy restriction (r = -0.26; p = 0.14). DISCUSSION: Fasting ghrelin concentrations did not rise after a 2-day energy restriction regimen. Moreover, changes in ghrelin concentrations during energy restriction were not associated with subsequent ad libitum food intake, suggesting that fasting ghrelin does not act as a hunger signal to the brain. The data did not support our hypothesis that leptin suppresses ghrelin levels.

Effect of a high-protein breakfast on the postprandial ghrelin response.

BACKGROUND: The most satiating macronutrient appears to be dietary protein. Few studies have investigated the effects of dietary protein on ghrelin secretion in humans. OBJECTIVE: This study was designed to investigate whether a high-protein (HP) breakfast is more satiating than a high-carbohydrate breakfast (HC) through suppression of postprandial ghrelin concentrations or through other physiologic processes. DESIGN: Fifteen healthy men were studied in a single-blind, crossover design. Blood samples and subjective measures of satiety were assessed frequently for 3 h after the consumption of 2 isocaloric breakfasts that differed in their protein and carbohydrate content (58.1% of energy from protein and 14.1% of energy from carbohydrate compared with 19.3% of energy from protein and 47.3% of energy from carbohydrate). The gastric emptying rate was indirectly assessed with the acetaminophen absorption test. RESULTS: The HP breakfast decreased postprandial ghrelin secretion more than did the HC breakfast (P < 0.01). Ghrelin concentrations were correlated with glucose-dependent insulinotropic polypeptide (r = -0.65; 95% CI: -0.85, -0.29) and glucagon concentrations (r = -0.47; 95% CI: -0.75, -0.03). Compared with the HC breakfast, the HP breakfast increased glucagon (P < 0.0001) and cholecystokinin (P < 0.01), tended to increase glucose-dependent insulinotropic polypeptide (P = 0.07) and glucagon-like peptide 1 (P = 0.10), and decreased the gastric emptying rate (P < 0.0001). Appetite ratings were not significantly different between the 2 treatments, and the HP breakfast did not significantly affect ad libitum energy intake. CONCLUSIONS: The HP breakfast decreased postprandial ghrelin concentrations more strongly over time than did the HC breakfast. High associations between ghrelin and glucose-dependent insulinotropic polypeptide and glucagon suggest that stimulation of these peptides may mediate the postprandial ghrelin response. The HP breakfast also reduced gastric emptying, probably through increased secretion of cholecystokinin and glucagon-like peptide 1.

Effects of gastric emptying on the postprandial ghrelin response.

Distension and chemosensitization of the stomach are insufficient to induce a ghrelin response, suggesting that postgastric feedback is required. This postgastric feedback may be regulated through insulin. We investigated the relation between gastric emptying rate and the postprandial ghrelin response as well as the role of insulin and other hormones possibly mediating this response. Fifteen healthy men [BMI 21.6 kg/m2 (SD 1.9), age 20.5 yr (SD 2.5)] were studied in a single-blind, crossover design. Subjects received two treatments separated by 1 wk: 1) a dairy breakfast in combination with a 3-h intravenous infusion of glucagon-like peptide-1 (GLP-1), which delays gastric emptying, and 2) a dairy breakfast in combination with a 3-h intravenous infusion of saline. Blood samples were drawn before breakfast and during the infusion. Postprandial ghrelin (total) responses were lower following the saline infusion compared with the GLP-1 infusion (P < 0.05). Acetaminophen concentrations, an indirect measurement of gastric emptying rate, were inversely correlated with total ghrelin concentrations (saline r = -0.76; 95% CI = -0.90, -0.49, GLP-1 r = -0.47; 95% CI = -0.76, -0.04). Ghrelin concentrations were only weakly correlated with insulin concentrations (saline r = -0.36; 95% CI = -0.69, 0.09; GLP- 1 r = -0.42; 95% CI = -0.73, 0.03), but strongly inversely correlated with GIP concentrations (saline r = -0.74; 95% CI= -0.89, -0.45; GLP-1 r = -0.63; 95% CI = -0.84, -0.27). In conclusion, our results support the hypothesis that ghrelin requires postgastric feedback, which may not be regulated through insulin. Conversely, our data suggest a role of glucose-dependent insulinotropic polypeptide in ghrelin secretion.

Ghrelin response to carbohydrate-enriched breakfast is related to insulin.

BACKGROUND: Ghrelin plays an important role in the regulation of food intake. Little is known about how ghrelin concentrations are modified by dietary factors. OBJECTIVE: We examined the effects of both amount and type of carbohydrate on ghrelin concentrations and all correlations among the variables ghrelin, glucose, insulin, leptin, and all 4 subjective measures of appetite. DESIGN: Twenty healthy nonobese men were studied in a double-blind, randomized, crossover design. Subjective measures of appetite and concentrations of ghrelin, glucose, insulin, and leptin were frequently assessed for 4 h after liquid breakfast meals differing in energy content and carbohydrate structure-ie, water, low-calorie (LC) meal, high-calorie simple carbohydrate (HC-SC) meal, and high-calorie complex carbohydrate (HC-CC) meal. RESULTS: Ghrelin concentrations decreased after the HC-SC breakfast by 41%, after the HC-CC breakfast by 33%, and after the LC breakfast by 24%. No significant differences in ghrelin concentration among the 3 breakfasts were observed until 120 min. Ghrelin concentrations were correlated with subjective measures of hunger (r=0.51) and fullness (r=-0.44). The percentage decrease in ghrelin between 0 and 30 min was inversely correlated with the percentage increases in insulin (r=-0.76) and glucose (r=-0.79) but not with changes in leptin (r=0.10). The percentage changes in ghrelin concentrations between 30 and 180 min were correlated with the percentage changes in insulin (r=-0.53) and leptin (r=-0.47) but not with changes in glucose (r=0.22). CONCLUSION: The results support the hypothesis that ghrelin requires postgastric feedback, which may be regulated through insulin.

Biomarkers of satiation and satiety.

This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding the regulation of food intake and energy balance. We made a distinction between biomarkers of satiation or meal termination and those of meal initiation related to satiety and between markers in the brain [central nervous system (CNS)] and those related to signals from the periphery to the CNS. Various studies showed that physicochemical measures related to stomach distension and blood concentrations of cholecystokinin and glucagon-like peptide 1 are peripheral biomarkers associated with meal termination. CNS biomarkers related to meal termination identified by functional magnetic resonance imaging and positron emission tomography are indicators of neural activity related to sensory-specific satiety. These measures cannot yet serve as a tool for assessing the satiating effect of foods, because they are not yet feasible. CNS biomarkers related to satiety are not yet specific enough to serve as biomarkers, although they can distinguish between extreme hunger and fullness. Three currently available biomarkers for satiety are decreases in blood glucose in the short term (<5 min), which have been shown to be involved in meal initiation; leptin changes during longer-term (>2-4 d) negative energy balance; and ghrelin concentrations, which have been implicated in both short-term and long-term energy balance. The next challenge in this research area is to identify food ingredients that have an effect on biomarkers of satiation, satiety, or both. These ingredients may help consumers to maintain their energy intake at a level consistent with a healthy body weight.