Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies. The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides. Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration. On the day before the intervention (day 0), a 380-cm multilumen tube (1.75-mm diameter) with independent port access to the duodenum and ileum was inserted, and position was confirmed by X-ray. Subsequently (days 1-4), a standardized breakfast meal was followed midmorning by a 90-min infusion of isotonic glucose (15 g, 235 kJ) or saline to the duodenum or ileum. Appetite ratings were assessed with the use of visual analog scales (VASs), blood samples collected, and ad libitum energy intake (EI) measured at lunch, afternoon snack, and dinner. Thirteen participants completed the 4 infusion days. There was a significant effect of nutrient infused and site (treatment × time, < 0.05) such that glucose-to-ileum altered VAS-rated fullness, satisfaction, and thoughts of food compared with saline-to-ileum (Tukey's post hoc, < 0.05); decreased ad libitum EI at lunch compared with glucose-to-duodenum [-22%, -988 ± 379 kJ (mean ± SEM), Tukey's post hoc, < 0.05]; and increased glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) compared with all other treatments (Tukey's post hoc, < 0.05). Macronutrient delivery to the proximal and distal small intestine elicits different outcomes. Glucose infusion to the ileum increased GLP-1 and PYY secretion, suppressed aspects of VAS-rated appetite, and decreased ad libitum EI at a subsequent meal. Although glucose to the duodenum also suppressed appetite ratings, eating behavior was not altered. This trial was registered at www.anzctr.org.au as ACTRN12612000429853.
Intermittent fasting improves metabolic and cardiac health. However, increased hunger towards the end of the fasting period may affect compliance and limit its application. Our aim was to determine the effect of anorexigenic agent co-therapy on subjective ratings of appetite during the 16–24 h period of a day-long water-only intermittent fast. Thirty adult men were recruited and required to fast for 24 h from 18:00 h to 18:00 h on the same day of the week for three subsequent weeks. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 100 mg) of a bitter hops-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast. From 18–24 h of the 24 h fast, both the HD and LD treatment groups exhibited a statistically significant (p < 0.05) > 10% reduction in hunger. Additionally, the expected lunchtime increase in hunger that was present in the placebo group (12:00 h) was absent in both the HD and LD groups. These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during intermittent fasting, and show that bitter compounds may regulate appetite independently of meal timing.
Background Gastrointestinal enteroendocrine cells express chemosensory bitter taste receptors (T2Rs) that may play an important role in regulating energy intake (EI) and gut function. Objectives To determine the effect of a bitter hop extract (Humulus lupulus L.) on acute EI, appetite and hormonal responses. Design Nineteen healthy-weight men completed a randomized three-treatment, double blind, cross-over study with a 1 week washout between treatments. Treatments comprised either placebo or 500 mg of hop extract administered in delayed release capsules (duodenal) at 1100 h or quick release capsules (gastric) at 1130 h. Ad libitum EI was recorded at the lunch (1200 h) and afternoon snack (1400 h), with blood samples taken and subjective ratings of appetite, gastrointestinal discomfort, vitality, meal palatability and mood assessed throughout the day. Results Total ad libitum EI was reduced following both the gastric (4473 kJ; 95% CI: 3811, 5134; P = 0.006) and duodenal (4439 kJ; 95% CI: 3777, 5102; P = 0.004) hop treatments compared with the placebo (5383 kJ; 95% CI: 4722, 6045). Gastric and duodenal treatments stimulated pre-lunch ghrelin secretion and post-prandial cholecystokinin, glucagon-like peptide 1 and peptide YY responses compared with placebo. In contrast, postprandial insulin, glucose-dependent insulinotropic peptide and pancreatic polypeptide responses were reduced in gastric and duodenal treatments without impacting glycemia. In addition, gastric and duodenal treatments produced small but significant increases in subjective measures of gastrointestinal discomfort (e.g., nausea, bloating, abdominal discomfort) with mild-severe adverse GI symptoms reported in the gastric treatment only. However, no significant treatment effects were observed for any subjective measures of appetite or meal palatability. Conclusion Both gastric and duodenal delivery of a hop extract modulates the release of hormones involved in appetite and glycemic regulation, providing a potential “bitter brake” on EI in healthy-weight men. Clinical Trial Registry: ACTRN12614000434695 www.anzctr.org.au.
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