We want to investigate whether bitter compounds, denatonium benzoate and quinine hydrochloride, have a distinct effect on gastrointestinal hormone release after infusion into the stomach or duodenum. Furthermore, we want to observe an effect on hunger sensations and hedonic food intake. Moreover, we suggest somatostatin as a driving factor for decreased motilin and ghrelin release after intragastric administration.
Intragastric administration of the bitter tastants denatonium benzoate (DB) or quinine hydrochloride (QHCl) decreases orexigenic hormone levels, and reduces hunger sensations. Contradictory, in vitro studies on human gastric and duodenal tissue showed that DB exposure increased motilin and octanoylated ghrelin levels. DB stimulated somatostatin (SST) release, which is an inhibiting paracrine hormone. We hypothesized that the reduction in hunger ratings and hormone levels is stronger after intragastric compared to intraduodenal administration, and that these differences are mediated by differential SST release. Fourteen healthy female volunteers participated in a randomized, placebo-controlled crossover study. After an overnight fast, DB (1 µmol/kg), QHCl (10 µmol/kg) or placebo were given intragastric or intraduodenal via a feeding tube. Blood samples were taken at regular time points to obtain the hormonal release. Hunger was rated at the same points on a 100 mm visual analog scale (VAS). Ad libitum milkshake intake was assessed at the end of the experiment and taste was scored on a VAS.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
14
A nasogastric feeding tube was positioned into the stomach, and checked with a pH strip. 10 µmol of quinine hydrochloride per kg body weight was administrated into the stomach.
A nasogastric feeding tube was positioned into the stomach, and checked with a pH strip. 1 µmol of denatonium benzoate per kg body weight was administrated into the stomach.
A nasogastric feeding tube was positioned into the stomach, and checked with a pH strip. 0.1 ml of water (placebo) per kg body weight was administrated into the stomach.
TARGID
Leuven, Vlaams-Brabant, Belgium
Changes in plasma levels of motilin, ghrelin, somatostatin, GLP-1 and CCK after bitter administration into the stomach or duodenum
Infusion of bitter compounds into the stomach or duodenum is performed via a nasogastric feeding tube. Afterwards, an intravenous dwelling line is placed to take blood samples at several time points during the experiment. Hormone levels of motilin, ghrelin, somatostatin, GLP-1 and CCK are collected with according enzyme inhibitors.
Time frame: A first blood sample is taken as a reference 10 min before administration of the condition. After the infusion, every 10 min blood samples are taken for 2 hours.
Changes in hunger scores after bitter administration into the stomach or duodenum
Infusion of bitter compounds into the stomach or duodenum is performed via a nasogastric feeding tube. Hunger is scored on a 100 mm visual analog scale at several time points during the experiment. Two hours after the infusion, the nasogastric feeding tube and intravenous dwelling line are removed and the subject drinks ad libitum from a chocolate milkshake until they are fully satisfied. Hunger is scored right before and after drinking the milkshake.
Time frame: Hunger is scored every 10 min during the whole experiment starting 20 min before the infusion, until 2 hours after the infusion. 1 minute before and after ad libitum drinking, hunger is scored.
Changes in hedonic food intake after bitter administration into the stomach or duodenum
Infusion of bitter compounds into the stomach or duodenum is performed via a nasogastric feeding tube. Two hours after the infusion of a bitter compound or placebo, the subjects drink ad libitum from a chocolate milkshake until they are fully satisfied. The milkshake is weighted before and after the experiment to calculate the amount of consumed calories (1 g milkshake = 1 kcal).
Time frame: 2 hours after the infusion of a condition, subjects drink from the milkshake without an intermission.
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A nasogastric feeding tube was positioned into the duodenum, and checked with fluoroscopy. 10 µmol of quinine hydrochloride per kg body weight was administrated into the duodenum.
A nasogastric feeding tube was positioned into the duodenum, and checked with fluoroscopy. 1 µmol of denatonium benzoate per kg body weight was administrated into the duodenum.
A nasogastric feeding tube was positioned into the duodenum, and checked with fluoroscopy. 0.1 ml of water (placebo) per kg body weight was administrated into the duodenum.