The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration

Abstract

Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill". However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: 1) the site of administration: intragastrically (IG) or intraduodenally (ID), 2) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and 3) the timing of infusion. Therefore, 14 healthy, female volunteers participated in a randomized, placebo-controlled six-visit crossover study. After an overnight fast, DB (1µmol/kg), QHCl (10µmol/kg) or placebo were given IG or ID via a nasogastric feeding tube. Blood samples were taken 10 min prior to administration and every 10 min after administration for a period of 2 hours. Hunger was rated at the same timepoints on a visual analogue scale (VAS). ID bitter administration did not affect hunger sensations, motilin or acyl-ghrelin release compared with its PLC infusion. IG QHCl infusion tended to suppress hunger increase, especially between 50-70 minutes after infusion, simultaneously with reduced motilin values. Here, acyl-ghrelin was not affected. IG DB did not affect hunger or motilin, however acyl-ghrelin levels were reduced 50-70 minutes after infusion. Plasma values of glucagon-like peptide 1 and cholecystokinin were too low to be properly detected or to have any physiological relevance. In conclusion, bitter tastants should be infused into the stomach to reduce hunger sensations and orexigenic gut peptides. QHCl has the best potential to reduce hunger sensations, and it should be infused 60 minutes before food intake.

Quinine Effects on Gut and Pancreatic Hormones and Antropyloroduodenal Pressures in Humans–Role of Delivery Site and Sex

“…While ID or IG administration cannot be used routinely, the insights may be pivotal for the design of formulations for targeted delivery. We did not measure plasma motilin, which is modulated by bitter substances ( 14 , 15 ), although IG, but not ID, QHCl appears to suppress motilin ( 17 ). We only assessed effects of quinine on fasting glucose; whether quinine lowers postprandial glucose in females more than in males warrants evaluation.…”

“…This is supported by the finding that small intestinal, but not gastric, exposure to nutrient (glucose) is sufficient to suppress plasma ghrelin ( 43 ). The recent report of a lack of effect of ID- or IG-QHCl on either plasma CCK or ghrelin may reflect the lower dose used ( 17 ), indicating dose-dependency. The suppressive effect of small intestinal nutrients or quinine on ghrelin release may, at least in part, be mediated by hormones.…”

“…A small number of studies have reported effects of quinine on the secretion of gut hormones, including suppression of plasma ghrelin, and stimulation of CCK and GLP-1 ( 12-16 ). Intragastric (IG) administration of quinine hydrochloride (QHCl), in a dose of 10 µmol/kg (equivalent to ~270 mg in a 70-kg human), suppressed ghrelin ( 14 , 15 ), while a recent study from the same group found no effect of either intraduodenal (ID) or IG-QHCl, in the same dose, on plasma CCK ( 17 ). In contrast, an IG bolus of 18 mg QHCl was found to increase plasma CCK (although the effect was very small) after a standardized meal ( 12 ).…”

Gastrointestinal hormones and regulation of gastric emptying

“…Variations in motilin release during the fasting state are closely related to the phase III contractions of the migrating motor complex (MMC) initiated in the stomach [7,9]. The role of motilin has not been completely explained yet; however, the recent discovery that motilin stimulates appetite has attracted much attention [10,11 ▪▪ ,12] (Fig. 1).…”

Mechanisms Underlying Food-Triggered Symptoms in Disorders of Gut-Brain Interactions

“…In FD, increased sensitivity to capsaicin administration has been reported, suggesting hypersensitivity to TRPV1 receptor activation ( 18 ). In healthy subjects, bitter tastants inhibit the release of motilin and ghrelin and suppress the occurrence of gastric phase 3, which is associated with decreased hunger sensations ( 19 , 20 ), but alterations in DGBI have not been studied to date. Low- or non-caloric sweeteners such as erythritol and xylitol do not alter plasma glucose or insulin levels, can stimulate the secretion of gut peptides such as CCK, GLP-1 and PYY, and slow down gastric emptying ( 21 , 22 ).…”