Effects of Intraduodenal Infusion of the Bitter Tastant, Quinine, on Antropyloroduodenal Motility, Plasma Cholecystokinin, and Energy Intake in Healthy Men

Abstract

Background/aims: Nutrient-induced gut hormone release (eg, cholecystokinin [CCK]) and the modulation of gut motility (particularly pyloric stimulation) contribute to the regulation of acute energy intake. Non-caloric bitter compounds, including quinine, have recently been shown in cell-line and animal studies to stimulate the release of gastrointestinal hormones by activating bitter taste receptors expressed throughout the gastrointestinal tract, and thus, may potentially suppress energy intake without providing additional calories. This study aims to evaluate the effects of intraduodenally administered quinine on antropyloroduodenal pressures, plasma CCK and energy intake.

Methods: Fourteen healthy, lean men (25 ± 5 years; BMI: 22.5 ± 2.0 kg/m2) received on 4 separate occasions, in randomized, double-blind fashion, 60-minute intraduodenal infusions of quinine hydrochloride at doses totaling 37.5 mg ("Q37.5"), 75 mg ("Q75") or 225 mg ("Q225"), or control (all 300 mOsmol). Antropyloroduodenal pressures (high-resolution manometry), plasma CCK (radioimmunoassay), and appetite perceptions/gastrointestinal symptoms (visual analog questionnaires) were measured. Ad libitum energy intake (buffet-meal) was quantified immediately post-infusion. Oral quinine taste-thresholds were assessed on a separate occasion using 3-alternative forced-choice procedure.

Results: All participants detected quinine orally (detection-threshold: 0.19 ± 0.07 mmol/L). Intraduodenal quinine did not affect antral, pyloric or duodenal pressures, plasma CCK (pmol/L [peak]; control: 3.6 ± 0.4, Q37.5: 3.6 ± 0.4, Q75: 3.7 ± 0.3, Q225: 3.9 ± 0.4), appetite perceptions, gastrointestinal symptoms or energy intake (kcal; control: 1088 ± 90, Q37.5: 1057 ± 69, Q75: 1029 ±7 0, Q225: 1077 ± 88).

Conclusions: Quinine, administered intraduodenally over 60 minutes, even at moderately high doses, but low infusion rates, does not modulate appetite-related gastrointestinal functions or energy intake.

Keywords: Cholecystokinin; Energy intake; Gastrointestinal hormones; Pylorus; Quinine.

Figure 1

Schematic representation of the study design. At t = −10 minutes, immediately after the occurrence of a phase III, ie, during phase I, with the multi-lumen manometric catheter positioned across the pylorus, a baseline blood sample was collected, and the participant completed a visual analogue scale (VAS) questionnaire for the assessment of appetite-related perceptions. The recording of pressures in the antropyloroduodenal region was also commenced. At t = 0 minutes, intraduodenal infusion of quinine hydrochloride at 37.5 mg (Q37.5), 75 mg (Q75), 225 mg (Q225), or control commenced for 60 minutes. During the infusion, antropyloroduodenal pressures were recorded continuously, and blood samples and VAS ratings were collected at 15-minute intervals. At t = 60 minutes, the intraduodenal infusion was terminated, and the catheter removed. The participant was then presented with a buffet-style meal and instructed to eat until he was comfortably full. At t = 90 minutes, another blood sample was collected, and a VAS questionnaire administered, after which the participant was free to leave the laboratory.

Figure 2

Scores for hunger (A), desire to eat (B), prospective food consumption (C), fullness (D), bloating (E), and nausea (F) during 60-minute intraduodenal infusions (t = 0–60 minutes) of quinine hydrochloride at 37.5 mg (Q37.5), 75 mg (Q75), 225 mg (Q225), or control, and after the buffet meal, at t = 90 minutes. Two-way ANOVAs, with treatment and time as factors, were used to assess differences between treatments. Post-hoc comparisons, adjusted for multiple comparisons by Bonferroni’s correction, were used to determine significant differences between either dose or control. Comparisons of post (t = 90 minutes) vs pre-meal (t = 60 minutes) data were done with Student’s paired t test. Data are expressed as means ± SEMs; n = 14. ID, intraduodenal.

Figure 3

Plasma cholecystokinin (A) and blood glucose (B) concentrations during 60-minute intraduodenal infusions (t = 0–60 minutes) of quinine hydrochloride at 37.5 mg (Q37.5), 75 mg (Q75), 225 mg (Q225), or control, and after the buffet meal, at t = 90 minutes. Data were analyzed using 2-way ANOVA, with treatment and time as factors. Comparison of post (t = 90 minutes) vs pre-meal (t = 60 minutes) concentrations were done with Student’s paired t test. Data are expressed as means ± SEMs; n = 14. ID, intraduodenal.